Macrophage procoagulant(s) is involved in cellular immunity and in pathological processes. The varied important functions and putative functions of procoagulant makes it worthy of study. Mouse exudate macrophages, whether stimulated with endotoxin in vitro or not, release factor VII-like activity into culture supernatants. A cell-bound factor, which appears to be tissue factor, is induced by endotoxin. The interaction of the cellular and supernatant factors results in a potent factor X activator. The cellular and supernatant factors have different metabolic requirements. Warfarin inhibits the production of the supernatant factor but does not affect the cellular factor. Tunicamycin and actinomycin D totally inhibit the induction of the cellular factor but have less effect on the supernatant factor. We now plan to study the following: (1)\The metabolic and functional effects of vitamin K1, chloro-K and warfarin on exudate macrophages, specifically concentrating on superoxide production, phagocytosis and 51Cr-labeled erythrocytes and tumoricidal and microbicidal activity; (2)\The effects of tunicamycin (an N-glycosylation inhibitor) on the process of macrophage activation and cell procoagulant production; (3)\The genetics of procoagulant production in response to LPS, concanavalin A, and antigen vis-a-vis the purported necessity for lymphocyte cooperativity; (4)\Investigate quantitatively the amount of procoagulant produced by monocyte macrophages at different levels of "activation" and test whether different levels of activation modulate the "lymphocyte requirement"; and (5)\Investigate the role of coagulant in the tumor necrosis reaction induced by TNF in Meth A tumor bearing mice. Modulation of the in vivo and in vitro activities will be attempted with warfarin and vitamin K1.